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Alternative Activation Is an Innate Response to Injury That Requires CD4 T Cells to be Sustained during Chronic Infection1
 

Summary: Alternative Activation Is an Innate Response to Injury That
Requires CD4 T Cells to be Sustained during Chronic Infection1
P'ng Loke,2
* Iain Gallagher,2
Meera G. Nair,3
Xingxing Zang,
Frank Brombacher,
Markus Mohrs,
James P. Allison,
and Judith E. Allen4
Alternatively activated macrophages (AAM ) are found in abundance during chronic Th2 inflammatory responses to
metazoan parasites. Important roles for these macrophages are being defined, particularly in the context of Th2-mediated
pathology and fibrosis. However, a full understanding of the requirements for alternative activation, particularly at the
innate level, is lacking. We present evidence that alternative activation by the Th2 cytokines IL-4 and IL-13 is an innate and
rapid response to tissue injury that takes place even in the absence of an infectious agent. This early response does not
require CD4 Th2 cells because it occurred in RAG-deficient mice. However, class II-restricted CD4 T cell help is essential
to maintain AAM in response to infection, because AAM were absent in RAG-deficient and MHC class II-deficient, but
not B cell-deficient mice after chronic exposure to the nematode parasite, Brugia malayi. The absence of AAM was
associated with increased neutrophilia and reduced eosinophilia, suggesting that AAM are involved in the clearance of
neutrophils as well as the recruitment of eosinophils. Consistent with this hypothesis, AAM show enhanced phagocytosis

  

Source: Allen, Judith - School of Biological Sciences, University of Edinburgh

 

Collections: Biology and Medicine